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Analysis of complement biomarkers in systemic sclerosis indicates a distinct pattern in scleroderma renal crisis

Okrój, Marcin LU ; Johansson, Martin LU ; Saxne, Tore LU ; Blom, Anna M. LU orcid and Hesselstrand, Roger LU (2016) In Arthritis Research and Therapy 18(1).
Abstract

Background: The complement system has been implicated in pathogenesis of systemic sclerosis (SSc). The goal of the present study was to evaluate improved complement biomarkers in SSc. Methods: The presence of C4d, reflecting activation of the classical/lectin pathways, C3bBbP corresponding to activation of the alternative pathway, and soluble terminal complement complexes (all complement pathways), was measured in plasma samples by enzyme-linked immunosorbent assay and correlated to clinical parameters. The study included 81 patients with limited cutaneous SSc and 41 with diffuse cutaneous SSc, as well as 47 matched healthy controls and 81 patients with rheumatoid arthritis, 22 with psoriatic arthritis and 20 with ankylosing... (More)

Background: The complement system has been implicated in pathogenesis of systemic sclerosis (SSc). The goal of the present study was to evaluate improved complement biomarkers in SSc. Methods: The presence of C4d, reflecting activation of the classical/lectin pathways, C3bBbP corresponding to activation of the alternative pathway, and soluble terminal complement complexes (all complement pathways), was measured in plasma samples by enzyme-linked immunosorbent assay and correlated to clinical parameters. The study included 81 patients with limited cutaneous SSc and 41 with diffuse cutaneous SSc, as well as 47 matched healthy controls and 81 patients with rheumatoid arthritis, 22 with psoriatic arthritis and 20 with ankylosing spondylitis. Skin and kidney biopsies of selected patients were stained to detect deposited C3b as a marker of local complement activation. Results: Biomarkers of activation of all complement pathways were increased in SSc compared with healthy controls and were similar to those in other rheumatic diseases. When patients with SSc were divided into subgroups, a distinct pattern of complement markers was observed in individuals with scleroderma renal crisis (SRC). By functional assay, we confirmed a significant decrease in complement haemolytic activity in SRC vs. non-SRC patients, indicating complement consumption. Further, we detected glomerular deposits of C3b in some patients with SRC. Conclusions: The data indicate that complement activation is an important feature of SRC.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Biomarkers, Complement, Renal crisis, Scleroderma, Systemic sclerosis
in
Arthritis Research and Therapy
volume
18
issue
1
article number
267
publisher
BioMed Central (BMC)
external identifiers
  • pmid:27863511
  • wos:000388416000002
  • scopus:84998775143
ISSN
1478-6354
DOI
10.1186/s13075-016-1168-x
language
English
LU publication?
yes
id
6009cf00-556c-426c-8939-0eb0ebdc80e4
date added to LUP
2016-12-19 12:52:56
date last changed
2024-11-03 11:09:40
@article{6009cf00-556c-426c-8939-0eb0ebdc80e4,
  abstract     = {{<p>Background: The complement system has been implicated in pathogenesis of systemic sclerosis (SSc). The goal of the present study was to evaluate improved complement biomarkers in SSc. Methods: The presence of C4d, reflecting activation of the classical/lectin pathways, C3bBbP corresponding to activation of the alternative pathway, and soluble terminal complement complexes (all complement pathways), was measured in plasma samples by enzyme-linked immunosorbent assay and correlated to clinical parameters. The study included 81 patients with limited cutaneous SSc and 41 with diffuse cutaneous SSc, as well as 47 matched healthy controls and 81 patients with rheumatoid arthritis, 22 with psoriatic arthritis and 20 with ankylosing spondylitis. Skin and kidney biopsies of selected patients were stained to detect deposited C3b as a marker of local complement activation. Results: Biomarkers of activation of all complement pathways were increased in SSc compared with healthy controls and were similar to those in other rheumatic diseases. When patients with SSc were divided into subgroups, a distinct pattern of complement markers was observed in individuals with scleroderma renal crisis (SRC). By functional assay, we confirmed a significant decrease in complement haemolytic activity in SRC vs. non-SRC patients, indicating complement consumption. Further, we detected glomerular deposits of C3b in some patients with SRC. Conclusions: The data indicate that complement activation is an important feature of SRC.</p>}},
  author       = {{Okrój, Marcin and Johansson, Martin and Saxne, Tore and Blom, Anna M. and Hesselstrand, Roger}},
  issn         = {{1478-6354}},
  keywords     = {{Biomarkers; Complement; Renal crisis; Scleroderma; Systemic sclerosis}},
  language     = {{eng}},
  month        = {{11}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Arthritis Research and Therapy}},
  title        = {{Analysis of complement biomarkers in systemic sclerosis indicates a distinct pattern in scleroderma renal crisis}},
  url          = {{http://dx.doi.org/10.1186/s13075-016-1168-x}},
  doi          = {{10.1186/s13075-016-1168-x}},
  volume       = {{18}},
  year         = {{2016}},
}